Mechanism of action
Triple CFTR modulator. Elexacaftor and tezacaftor are correctors that help misfolded CFTR protein (e.g., F508del) reach the cell surface; ivacaftor is a potentiator that holds the channel open. Restores chloride and bicarbonate transport, thinning airway secretions.
Dosing
- Adult
- Age ≥12: two tablets (elexacaftor 100 mg / tezacaftor 50 mg / ivacaftor 75 mg) in the morning and one ivacaftor 150 mg tablet in the evening, about 12 hours apart, with fat-containing food
- Pediatric
- Age 2–11: weight-based tablets or granules
Reduce dose with moderate or strong CYP3A inhibitors (e.g., ketoconazole, clarithromycin). Avoid grapefruit.
Indications
- Cystic fibrosis (age ≥2) with at least one F508del mutation or another CFTR mutation shown to respond
Contraindications
- Severe hepatic impairment (Child-Pugh C) — not recommended
- Use with strong CYP3A inducers (rifampin, carbamazepine, phenytoin, St John's wort) — not recommended
Side effects
- Raised transaminases and bilirubin; drug-induced liver injury, including rare liver failure
- Rash
- Headache, upper respiratory symptoms, abdominal pain, diarrhea
- Raised creatine kinase
- Non-congenital cataracts in children
Monitoring parameters
- Liver function tests at baseline, every 3 months in year 1, then yearly
- Eye examinations in children (cataracts)
- Sweat chloride, FEV1, weight
Drug interactions
- CYP3A inducers lower levels (avoid)
- CYP3A inhibitors raise levels (dose reduction)
- Grapefruit juice